Hypoxia-induced activation of KATP channels limits energy depletion in the guinea pig heart.

Abstract

The functional role of ATP-dependent potassium (KATP) in hypoxic cardiac failure was investigated in isolated guinea pig hearts with glibenclamide and rimalkalim as inhibitor and activator, respectively. Monophasic action potential duration at 90% of repolarization (MAP50), left ventricular function, and cardiac energy status (31P nuclear magnetic resonance spectroscopy) were measured during normotoxic (95% O2) and hypoxic (20% O2) perfusion. In normoxic hearts, 1 microM glibenclamide did not affect MAP50, left ventricular function, and coronary flow (n = 4). In contrast, rimalkalim rapidly shortened MAP50 and left ventricular pressure (LVP) in a dose-dependent fashion (e.g., by 60.2 +/- 3.5 and 80.8 +/- 8.2%, respectively, with 0.6 microM rimalkalim). This latter effect was reversed by 1 microM (glibenclamide (n = 4). With hypoxic perfusion, a reduction in LVP was observed, along with a shortening of the action potential (MAP90; 202 +/- 13 vs. 164 +/- 9 ms) and an increase in coronary flow. Glibenclamide (1 microM) reversed the MAP90 shortening and the increase in coronary flow. In addition, glibenclamide increased LVP transiently (n = 4). When coronary flow of hypoxic hearts was kept constant, however, glibenclamide elicited a sustained positive inotropic effect (n = 7). After glibenclamide, an increase in LVP from 54 +/- 4 to 64 +/- 3 mmHg was observed, along with a reduction in the free energy change of ATP hydrolysis from -54.5 +/- 1.9 to -52.9 +/- 0.2 nJ/mol and a further increase in the coronary venous adenosine from 269 +/- 48 to 1,680 +/- 670 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: U K Decking, T Reffelmann, J Schrader, H Kammermeier
• Journal: The American journal of physiology (Am J Physiol) Vol. 269 Issue 2 Pt 2 Pg. H734-42 (Aug 1995) ISSN: 0002-9513 [Print] United States
• PMID: 7653639 (Publication Type: Journal Article)

Chemical References

• Potassium Channel Blockers
• Potassium Channels
• Adenosine Triphosphate
• Glyburide

Topics

• Adenosine Triphosphate (physiology)
• Animals
• Energy Metabolism
• Female
• Glyburide (pharmacology)
• Guinea Pigs
• Hypoxia (metabolism)
• Myocardium (metabolism)
• Potassium Channel Blockers
• Potassium Channels (physiology)
• Reference Values